Age associated increases occur in many malignancies including lymphoma, leukemias and myeloma. Bone marrow transplantation (BMT) has been successfully utilized to treat neoplastic conditions in younger individuals. However, due to the increased risk of developing graft-versus-host disease (GVHD) in older patients, this procedure is generally not used in patients over the age of 60. Recent findings from our laboratory have demonstrated that intermediate age (12-14 mo) recipient mice develop a more severe course of acute GVHD than young adult recipients (2-3 mo) following allogeneic BMT. Furthermore, it has been demonstrated that pretransplant conditioning with irradiation induces the production of proinflammatory cytokine and increased mortality in young animals. The goals of this proposal are to determine the effects of pretransplant irradiation conditioning in mice of increasing age which could participate in an enhanced GVHD process in older recipients. T lymphocytes present in the donor spleen cell inoculum are responsible for the induction of GVHD. The effect of donor spleen cell dose on the development of GVHD in old (23-25 mo), intermediate and young recipients will be analyzed to further demonstrate that old recipient animals develop a more severe course of GVHD than the younger counterparts. It has been demonstrated experimentally and clinically that pretransplant conditioning with irradiation predisposes BMT recipients to heightened responsiveness via the induction of proinflammatory cytokines. Experiments will be designed to determine if older recipients produce increased levels of proinflammatory cytokines following exposure to irradiation via the induction of reactive oxygen intermediates. Additionally, experiments are proposed to test the hypothesis that increased expression of cellular adhesion molecules in older mice following exposure to pretransplant condition may result in enhanced homing of effector lymphoid cells to the GVHD target tissues, resulting in the enhanced GVHD process. The ability to identify the deleterious characteristics which develop in recipients of increasing age following conditioning may lead to effective therapies to alter the enhanced GVHD which develops in older animals and patients.